Cardio Notes: Feds Eying PLATO Results

The pivotal trial supporting the approval of ticagrelor (Brilinta) is being investigated by U.S. authorities, and the appropriate length of dual antiplatelet therapy after implantation of a drug-eluting stent will be evaluated.

PLATO Under Scrutiny

AstraZeneca, which makes ticagrelor, announced last week that the U.S. Department of Justice has issued a "civil investigative demand" for information regarding the PLATO trial.

A spokesperson for the drug maker declined to provide details about what the DOJ is looking for, and said the company "intends to cooperate with the inquiry." The spokesperson also said that the company stands behind the PLATO trial and the role of ticagrelor, pointing to the guidance of a 10-member academic group for the conduct of the trial, the oversight of an independent data safety monitoring board, and the review by the FDA before the drug was approved for patients with acute coronary syndromes in 2011.

Abbott announced that it will initiate a clinical trial to evaluate whether 3 months of dual antiplatelet therapy (DAPT) after implantation of one of its Xience family of everolimus-eluting stents is sufficient.

The purpose of the trial -- which has a planned enrollment of 4,000 patients -- "is to support regulatory filings to update the product labeling" for the Xience stents in the U.S., where DAPT is recommended for at least 12 months after implantation of a drug-eluting stent.

An ongoing 20,000-patient study – the DAPT trial – is exploring the relative risks and benefits of DAPT for 12 or 30 months.

Insulin Therapy Tied to Worse Revascularization Outcomes

Among diabetics with multivessel coronary artery disease, insulin treatment was associated with worse outcomes after CABG or percutaneous coronary intervention (PCI) with drug-eluting stents, an analysis of the FREEDOM trial showed.

About a third (32.5%) of the patients who underwent revascularization in the trial required insulin treatment at baseline. The rate of all-cause death, stroke, or myocardial infarction at 5 years was significantly higher in these patients compared with those who didn't require insulin (29% versus 19%; HR 1.63, 95% CI 1.32-2.02). The insulin-treated patients also had higher rates of cardiovascular death and 1-year revascularization.

The main findings from the FREEDOM trial – reductions in the rates of all-cause death and MI and an increase in the rate of stroke in the CABG group – remained consistent in both the insulin-treated and non-insulin-treated patients, Michael Farkouh, MD, of the Icahn School of Medicine at Mount Sinai in New York City, reported at a press briefing at the TCT meeting.

Checking Genetic Profile Improves DAPT Effect in Poor Responders

Adjusting the DAPT regimen when genetic information revealed a poor response to clopidogrel resulted in clinical outcomes similar to those in patients who had a normal or enhanced response to the drug, a French study showed.

In the study, patients who underwent primary PCI for an acute MI were genotyped to look for markers of poor clopidogrel response; 22% were found to carry an allele associated with slow or very slow metabolism of the drug. That information was given to the treating physicians along with recommendations to switch the poor metabolizers to prasugrel (Effient) or a double dose of clopidogrel if there was a contraindication to the more potent drug.

Of the poor metabolizers, 85% had their DAPT regimen adjusted. At 1 year, these patients had a rate of death, MI, or stent thrombosis that was comparable with that in the patients with a normal or enhanced response to clopidogrel (3.04% versus 3.3%). The poor metabolizers who did not have an adjustment, however, had significantly worse outcomes (15.6% versus 3.04%). There were no differences in major bleeding across the groups, Bernard Chevalier, MD, of the Institut Cardiovasculaire Paris Sud, reported at the TCT meeting.

No Big Impact From Platelet Function Testing in Clinical Practice

The provision of free platelet function assays increased use of the tests at hospitals treating patients with acute coronary syndromes, but the resulting information did not often induce a change in DAPT regimen, the TRANSLATE-POPS trial showed.

In the cluster-randomized trial -- reported by Tracy Wang, MD, of the Duke Clinical Research Institute at the TCT meeting -- half of the centers received the VerifyNow P2Y12 test for free and were encouraged to use it in their patients, and the rest of the centers did not receive any intervention. Any decisions made on the basis of the results were left to the treating physicians.

Platelet function testing was performed in only 1.4% of the control hospitals and in 66.4% of the intervention hospitals. Therapeutic adjustments – an increase in dose or a switch to another drug -- occurred at a higher rate in the hospitals provided the tests for free, but such adjustments were not very frequent in either group (15.9% versus 11.6%, P=0.01).

Through 30 days, the rate of major adverse cardiovascular events was not significantly different between the intervention and control arms (4.5% versus 5.1%, P=0.69), consistent with previous randomized trials that have failed to show a benefit from adjusting antiplatelet therapy on the basis of platelet function testing.

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